Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2+ Gastric Cancer (DESTINY-Gastric03)

Official Title

A Phase 1b/2 Multicentre, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumour Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants With HER2 Overexpressing Gastric Cancer (DESTINY-Gastric03)

Summary:

DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumour activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or durvalumab in HER2-positive advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma patients.

Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or durvalumab administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumour efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-positive gastric/GEJ cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.

Trial Description

Primary Outcome:

• Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
• Part 2: Objective Response Rate (ORR)

• Part 1: Objective Response Rate (ORR)
• Part 2: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
• Duration of Response (DoR)
• Disease Control Rate (DCR)
• Progression Free Survival (PFS)
• Overall survival (OS)
• Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms
• Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
• Presence of ADAs for T-DXd and durvalumab (in study arms including T-DXd and durvalumab)

View this trial on ClinicalTrials.gov